LC-MS/MS法测定磷酸特地唑胺中2种基因毒性杂质  

Determination of two genotoxic impurities in terzolamide phosphate by LC-MS/MS

作　　者：苏爽 杨继伟 徐巧 李剑 俞晓峰 Su Shuang;Yang Jiwei;Xu Qiao;Li Jian;Yu Xiaofeng(Expec Technology Inc.,Hangzhou 311300)

机构地区：[1]杭州谱育科技发展有限公司,杭州311300

出　　处：《中国抗生素杂志》2025年第1期65-69,共5页Chinese Journal of Antibiotics

摘　　要：目的建立超高效液相色谱-串联质谱法测定磷酸特地唑胺中2种基因毒性杂质的含量。方法样品使用稀释液(0.5%氨水)溶解后采用Waters BEH C18色谱柱;以0.1%甲酸水(A)、0.1%甲酸乙腈(B)为流动相,梯度洗脱,流速为0.3 mL/min,柱温为40℃;采用电喷雾离子源(ESI)正离子扫描,多反应监测(MRM)模式对2种杂质进行定量检测。结果2种杂质在0.375~30μg/L范围内具有良好的线性关系;检出限分别为0.09和0.05μg/L;定量限分别为0.375和0.188μg/L;2种杂质在磷酸特地唑胺中,25%限度、50%限度、100%限度和150%限度的加标回收率(n=3)在96.9%~129.6%之间,回收率RSD小于5%。结论对磷酸特地唑胺片和原料药中杂质进行检测,杂质主要来源于原料药,两种杂质总量均未超过限值。该方法灵敏度高、专属性好,准确度高,可用于测定磷酸特地唑胺中2种基因毒性杂质,为磷酸特地唑胺的质量控制提供技术支持。Objective To establish a method for the determination of two genotoxic impurities in tedizolid phosphate by ultra-high performance liquid chromatography-tandem mass.Methods The samples were dissolved in diluent(0.5%ammonia solution),and then the chromatography was performed on the Waters BEH C18 column.Using 0.1%formic acid water(mobile phase A)and 0.1%formic acid acetonitrile(mobile phase B)as mobile phases,gradient elution was performed at a flow rate of 0.3 mL/min.The column temperature was set at 40 oC.The compounds were scanned by positive ion ESI,and the two impurities were quantitatively detected in multiple reaction monitoring(MRM)mode.Results The two impurities had a good linear relationship in the range of 0.375~30μg/L.The detection limits were 0.09 and 0.05μg/L,respectively.The limits of quantitation were 0.375 and 0.188μg/L,respectively.The recoveries(n=3)of 25%limit standard addition level,50%limit standard addition level,100%limit standard addition level and 150%limit standard addition level of the two impurities in terezolamide phosphate were between 96.9%and 129.6%,and the RSD of the two impurities was less than 5%in the terezolamide phosphate.Conclusion Impurities in terazolamide phosphate tablets and raw materials were detected,and the impurities mainly came from the raw materials.The total amount of both impurities did not exceed the limit.The method had high sensitivity,specificity and accuracy,which can be used for the determination of two genotoxic impurities in terzolamide phosphate,providing technical support for the quality control of terzolamide phosphate.

关 键 词：磷酸特地唑胺 恶唑烷酮类 基因毒性杂质 液相色谱-串联质谱 

分 类 号：R917[医药卫生—药物分析学]